Mycophenolate Mofetil (MMF) is an effective immunosuppressant used in kidney transplant recipients to prevent acute rejection. Complications such as diarrhea, leukopenia, and infections may necessitate the reduction or discontinuation of MMF. The objective of the study was to investigate the prevalence, timing, and reasons for MMF discontinuation and its association with outcomes in pediatric kidney transplant recipients.

Methods

Seven Pediatric Nephrology Research Consortium (PNRC) centers participated in a retrospective analysis of kidney transplant recipients <21 years of age. Characteristics and outcomes of patients in whom MMF was discontinued were compared to those who continued taking MMF throughout the first 2 years post-transplant.

Results

The study population included 288 participants (mean age 11.2 years) from 7 North American transplant centers. MMF was discontinued in 93/288 (32%) of participants. Common reasons for discontinuation included infections (35%), diarrhea (32%), leukopenia (15%), and others (18%). Increased cumulative alloimmunity (55% vs. 42%, p = .02), increased number of hospitalizations (82% vs. 67%, p = .01), and viral replications (79% vs. 47%, p < .0001) were observed in the MMF discontinuation group compared to the continuation group. Greater eGFR decline also occurred in the MMF discontinuation group over 2 years of follow-up (−7 vs. −1 mL/min/1.73 m², p = .05).

Conclusions

Almost a third of pediatric kidney transplant recipients who begin MMF for maintenance immunosuppression have it discontinued within the first 2 years post-transplant, and this subset of patients is more likely to experience adverse outcomes. New strategies are needed to manage MMF therapy and improve post-transplant outcomes.

Open Research

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon reasonable request.

REFERENCES

1Mendez R. FK 506 and mycophenolate mofetil in renal transplant recipients: six-month results of a multicenter, randomized dose ranging trial. FK 506 MMF Dose-Ranging Kidney Transplant Study Group. Transplant Proc. 1998; 30(4): 1287-1289.
10.1016/S0041-1345(98)00244-9
CAS PubMed Web of Science® Google Scholar
2Wuthrich RP, Weinreich T, Ambuhl PM, Schwarzkopf AK, Candinas D, Binswanger U. Reduced kidney transplant rejection rate and pharmacoeconomic advantage of mycophenolate mofetil. Nephrol Dial Transplant. 1999; 14(2): 394-399.
10.1093/ndt/14.2.394
CAS PubMed Web of Science® Google Scholar
3Pelletier RP, Akin B, Henry ML, et al. The impact of mycophenolate mofetil dosing patterns on clinical outcome after renal transplantation. Clin Transplant. 2003; 17(3): 200-205.
10.1034/j.1399-0012.2003.00026.x
PubMed Web of Science® Google Scholar
4Knoll GA, MacDonald I, Khan A, Van Walraven C. Mycophenolate mofetil dose reduction and the risk of acute rejection after renal transplantation. J Am Soc Nephrol. 2003; 14(9): 2381-2386.
10.1097/01.ASN.0000079616.71891.F5
CAS PubMed Web of Science® Google Scholar
5Bunnapradist S, Ambuhl PM. Impact of gastrointestinal-related side effects on mycophenolate mofetil dosing and potential therapeutic strategies. Clin Transplant. 2008; 22(6): 815-821.
10.1111/j.1399-0012.2008.00892.x
CAS PubMed Web of Science® Google Scholar
6Ensley RD, Bristow MR, Olsen SL, et al. The use of mycophenolate mofetil (RS-61443) in human heart transplant recipients. Transplantation. 1993; 56(1): 75-82.
10.1097/00007890-199307000-00013
CAS PubMed Web of Science® Google Scholar
7Kitchin JE, Pomeranz MK, Pak G, Washenik K, Shupack JL. Rediscovering mycophenolic acid: a review of its mechanism, side effects, and potential uses. J Am Acad Dermatol. 1997; 37(3 Pt 1): 445-449.
10.1016/S0190-9622(18)30747-3
CAS PubMed Web of Science® Google Scholar
8Reinke P, Budde K, Hugo C, et al. Reduction of gastrointestinal complications in renal graft recipients after conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium. Transplant Proc. 2011; 43(5): 1641-1646.
10.1016/j.transproceed.2011.01.184
CAS PubMed Web of Science® Google Scholar
9Schwartz GJ, Work DF. Measurement and estimation of GFR in children and adolescents. Clin J Am Soc Nephrol. 2009; 4(11): 1832-1843.
10.2215/CJN.01640309
PubMed Web of Science® Google Scholar
10Levey AS, Coresh J, Greene T, et al. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med. 2015; 145(4): 247-254.
10.7326/0003-4819-145-4-200608150-00004
Google Scholar
11Cook C, Scott AW, Leger K, Somers MJ. Non-protocol immunosuppression changes during the first year after kidney transplantation. Pediatr Transplant. 2017; 21(S1): p76 (Abstract 260).
Google Scholar
12Lederer SR, Friedrich N, Banas B, Welser G, Albert ED, Sitter T. Effects of mycophenolate mofetil on donor-specific antibody formation in renal transplantation. Clin Transplant. 2005; 19(2): 168-174.
10.1111/j.1399-0012.2005.00261.x
PubMed Web of Science® Google Scholar

Citing Literature

Volume28, Issue1

February 2024

e14628

Prevalence of mycophenolate mofetil discontinuation and subsequent outcomes in pediatric kidney transplant recipients: A PNRC study

Abstract

Background

Methods

Results

Conclusions

Open Research

DATA AVAILABILITY STATEMENT

REFERENCES

Citing Literature

References

Information

About Wiley Online Library

Help & Support

Opportunities

Connect with Wiley

Prevalence of mycophenolate mofetil discontinuation and subsequent outcomes in pediatric kidney transplant recipients: A PNRC study

Abstract

Background

Methods

Results

Conclusions

Open Research

DATA AVAILABILITY STATEMENT

REFERENCES

Citing Literature

References

Related

Information